title: A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma.
abstract: OBJECTIVE
  Complement may play a role in the clinical response to rituximab and other monoclonal antibody-based therapies of cancer. The purpose of this study was to explore the relationship between the C1qA([276]) polymorphism and the clinical response to rituximab in patients with follicular lymphoma.
  
  
  METHODS
  Genotyping for C1qA([276A/G]) was done in 133 subjects with follicular lymphoma treated with single-agent rituximab, and correlation with clinical response was done using Cox regression analysis.
  
  
  RESULTS
  Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the A allele compared with homozygous G subjects. Homozygous G subjects had a time to progression of 282 days, whereas A-allele carriers had a time to progression of 708 days [hazard ratio, (HR), 2.5; 95% confidence interval (95% CI), 2.0-3.1; P = 0.02]. Among subjects who achieved complete remission, homozygous G subjects had a time to progression of 250 days, whereas A-allele carriers had a time to progression of 1,118 days (HR, 4.5; 95% CI, 4.1-4.8, P = 0.04). The difference persisted after controlling for CD32 and CD16 polymorphisms. In patients who responded to rituximab used as first-line agent, a linear trend was observed among the C1qA([276]) genotypes, with homozygous A subjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects.
  
  
  CONCLUSIONS
  Our findings indicate that polymorphisms in the C1qA gene may affect the clinical response and duration of response to rituximab therapy of follicular lymphoma. These results could have direct implications on designing antibodies with improved efficiency and enhance our understanding of the role of complement in monoclonal antibody therapy.
authors.affiliation: Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa 52242, USA. emil-racila@uiowa.edu
authors.forename: Emilian
authors.initials: E
authors.lastname: Racila
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Weng
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Stephen
authors.initials: S
authors.lastname: Ansell
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Christopher
authors.initials: C
authors.lastname: Dahle
authors.forename: Ahmad
authors.initials: A
authors.lastname: Halwani
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
authors.forename: George J
authors.initials: GJ
authors.lastname: Weiner
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015922:Complement C1q / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012074:Remission Induction; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D015922:Complement C1q